The country music version was originally to have been recorded as a duet with Keith Urban, who was also to play banjo on the song. After Jon Bon Jovi decided that Urban's voice was too similar to his own, he asked a representative of Mercury Records to recommend a female duet partner.[2][3]

The music video for the country version features Habitat for Humanity volunteers, including members of the Philadelphia SoulArena Football League team owned in part by Jon Bon Jovi, building homes for low-income families and was used to promote the organization while another version of music video features a man in a dog pursuit. It also received an award for Best Collaborative Video at the CMT Music Awards in 2006. The Jennifer Nettles version has the same setting.

During the 2008 US Presidential election, the original version of "Who Says You Can't Go Home" was used frequently at public events supporting the Republican Party. Specifically, the song was a prominent feature at several large rallies supporting vice-presidential candidate and former Governor of AlaskaSarah Palin. This use of the song quickly became part of a controversy over several different songs that Republican candidates had been using without the artists permission, including music by Foo Fighters, Heart, John Mellencamp, and Boston. The Republicans, in turn, claimed "blanket rights" to play the songs at their public events.

In launching the complaint, Bon Jovi stated,

"We were not asked... we do not approve of their use of [the song]. We wrote this song as a thank you to those who have supported us over the past 25 years. The song has since become a banner for our home state of New Jersey and the de facto theme song for our partnerships around the country to build homes and rebuild communities."

Bon Jovi has been an enthusiastic Democratic Party supporter, appearing at a $30,000 per-plate fundraiser in support of President Barack Obama and performing at rallies for various Democratic candidates.